Abstinence-Induced Nicotine Seeking Relays on a Persistent Hypoglutamatergic State within the Amygdalo-Striatal Neurocircuitry

Nicotine robustly sustains smoking behavior by acting as a primary reinforcer and by enhancing the incentive salience of the nicotine-associated stimuli. The motivational effects produced by environmental cues associated with nicotine delivery can progressively manifest during abstinence resulting in reinstatement of nicotine seeking. However, how the activity in reward neuronal circuits is transformed during abstinence-induced nicotine seeking is not yet fully understood. In here we used a contingent nicotine and saline control self-administration model to disentangle the contribution of cue-elicited seeking responding for nicotine after drug abstinence in male Wistar rats. Using ex vivo electrophysiological recordings and a network analysis approach, we defined temporal and brain-region specific amygdalo-striatal glutamatergic alterations that occur during nicotine abstinence. The results from this study provide critical evidence indicating a persistent hypoglutamatergic state within the amygdalo-striatal neurocircuitry over protracted nicotine abstinence. During abstinence-induced nicotine seeking, electrophysiological recordings showed progressive neuroadaptations in dorsal and ventral striatum already at 14-d abstinence while neuroadaptations in subregions of the amygdala emerged only after 28-d abstinence. The observed neuroadaptations pointed to a brain network involving the amygdala and the dorsolateral striatum (DLS) to be implied in cue-induced reinstatement of nicotine seeking. Together these data suggest long-lasting neuroadaptations that might reflect neuroplastic changes responsible to abstinence-induced nicotine craving. Neurophysiological transformations were detected within a time window that allows therapeutic intervention advancing clinical development of preventive strategies in nicotine addiction. </p

Hyperglycemia and lower diet quality in pregnant overweight women and increased infant size at birth and at 13 months of age - STEPS study

Conclusions: Maternal prepregnancy overweight increases risk of hyperglycemia in late-pregnancy and increased infant size at birth and 13 months possibly predisposing the infant to health risks later in life. (C) 2013 Elsevier Ireland Ltd. All rights reserved.</p

Longitudinal child-oriented dietary intervention : Association with parental diet and cardio-metabolic risk factors. The Special Turku Coronary Risk Factor Intervention Project

Background: The child-oriented dietary intervention given in the prospective Special Turku Coronary Risk Factor Intervention Project (STRIP) has decreased the intake of saturated fat and lowered serum cholesterol concentration in children from infancy until early adulthood. In this study, we investigated whether the uniquely long-term child-oriented intervention has affected also secondarily parental diet and cardio-metabolic risk factors. Methods: The STRIP study is a longitudinal, randomized infancy-onset atherosclerosis prevention trial continued from the child's age of 8 months to 20 years. The main aim was to modify the child's diet towards reduced intake of saturated fat. Parental dietary intake assessed by a one-day food record and cardio-metabolic risk factors were analysed between the child's ages of 9-19 years. Results: Saturated fat intake of parents in the intervention group was lower [mothers: 12.0 versus 13.9 daily energy (E%), p Conclusions: Child-oriented dietary intervention shifted the dietary fat intakes of parents closer to the recommendations and tended to decrease total and low-density lipoprotein cholesterol in the intervention mothers. Dietary intervention directed to children benefits also parents.Peer reviewe

Stepping Up Telehealth: Using telehealth to support a new model of care for type 2 diabetes management in rural and regional primary care

Our proposal is to pilot the feasibility and acceptability of a telehealth intervention to enhance care in rural general practice for people with out-of-target Type 2 Diabetes (T2D). Our research program builds on the UK Medical Research Council framework in developing a model of care intervention that is well matched to the setting of General Practice and to the experiences and priorities of patients. We undertook an exploratory qualitative study, leading to the development of a practice-based intervention that we pilot tested for feasibility and acceptability before undertaking a larger pilot and a cluster RCT. We based our work on Normalisation Process Theory (NPT), a sociological theory of implementation, which describes how new practices become incorporated into routine clinical care as a result of individual and collective work. NPT suggested that our model of care intervention would need to be patient centred and include all members of the multidisciplinary diabetes team, including Endocrinologist, RN-CDE General Practitioners (GP), and generalist Practice Nurses (PNs). All of these groups are involved in the �work� of insulin initiation.The research reported in this paper is a project of the Australian Primary Health Care Research Institute which is supported by a grant from the Australian Government Department of Health and Ageing under the Primary Health Care Research Evaluation and Development Strategy

Pleasantness, familiarity, and identification of spice odors are interrelated and enhanced by consumption of herbs and food neophilia

The primary dimension of odor is pleasantness, which is associated with a multitude of factors. We investigated how the pleasantness, familiarity, and identification of spice odors were associated with each other and with the use of the respective spice, overall use of herbs, and level of food neophobia. A total of 126 adults (93 women, 33 men; age 25-61 years, mean 39 years) rated the odors from 12 spices (oregano, anise, rosemary, mint, caraway, sage, thyme, cinnamon, fennel, marjoram, garlic, and clove) for pleasantness and familiarity, and completed a multiple-choice odor identification. Data on the use of specific spices, overall use of herbs, and Food Neophobia Scale score were collected using an online questionnaire. Familiar odors were mostly rated as pleasant (except garlic), whereas unfamiliar odors were rated as neutral (r = 0.63). We observed consistent and often significant trends that suggested the odor pleasantness and familiarity were positively associated with the correct odor identification, consumption of the respective spice, overall use of herbs, and food neophilia. Our results suggest that knowledge acquisition through repetitive exposure to spice odor with active attention may gradually increase the odor pleasantness within the framework set by the chemical characteristics of the aroma compound. (C) 2016 Elsevier Ltd. All rights reserved.Peer reviewe

Driver Gene and Novel Mutations in Asbestos-Exposed Lung Adenocarcinoma and Malignant Mesothelioma Detected by Exome Sequencing

Background Asbestos is a carcinogen linked to malignant mesothelioma (MM) and lung cancer. Some gene aberrations related to asbestos exposure are recognized, but many associated mutations remain obscure. We performed exome sequencing to determine the association of previously known mutations (driver gene mutations) with asbestos and to identify novel mutations related to asbestos exposure in lung adenocarcinoma (LAC) and MM. MethodsExome sequencing was performed on DNA from 47 tumor tissues of MM (21) and LAC (26) patients, 27 of whom had been asbestos-exposed (18 MM, 9 LAC). In addition, 9 normal lung/blood samples of LAC were sequenced. Novel mutations identified from exome data were validated by amplicon-based deep sequencing. Driver gene mutations in BRAF, EGFR, ERBB2, HRAS, KRAS, MET, NRAS, PIK3CA, STK11, and ephrin receptor genes (EPHA1-8, 10 and EPHB1-4, 6) were studied for both LAC and MM, and in BAP1, CUL1, CDKN2A, and NF2 for MM. ResultsIn asbestos-exposed MM patients, previously non-described NF2 frameshift mutation (one) and BAP1 mutations (four) were detected. Exome data mining revealed some genes potentially associated with asbestos exposure, such as MRPL1 and SDK1. BAP1 and COPG1 mutations were seen exclusively in MM. Pathogenic KRAS mutations were common in LAC patients (42 %), both in non-exposed (n = 5) and exposed patients (n = 6). Pathogenic BRAF mutations were found in two LACs. ConclusionBAP1 mutations occurred in asbestos-exposed MM. MRPL1, SDK1, SEMA5B, and INPP4A could possibly serve as candidate genes for alterations associated with asbestos exposure. KRAS mutations in LAC were not associated with asbestos exposure.Peer reviewe

Sexually Dimorphic Associations between Maternal Factors and Human Milk Hormonal Concentrations

While human milk composition is characterised by marked dynamicity, we are far from having a clear picture of what factors drive this variation. Hormones in human milk are known to vary according to specific maternal phenotypes, but limited evidence shows the infant also has a role in determining milk composition. The present study aimed to investigate the interplay between maternal and infant characteristics in relation to human milk hormonal profile. In total, 501 human milk samples from mothers recruited in the Finnish STEPS cohort study (Steps to the healthy development) were analysed. Pre-pregnancy and pregnancy maternal data, socioeconomic status and infant characteristics at birth were collated. Leptin, adiponectin, insulin-like growth factor-1 and cyclic Glycine-Proline in milk were measured. Multivariate analysis of variance (MANOVA) and linear regression were utilised for statistical analysis. Sex-specific interactions with maternal factors were observed, as the infant sex mediated associations between gestational diabetes and milk adiponectin (p = 0.031), birth-mode and total protein (p = 0.003), maternal education and insulin-like growth factor-1: cyclic Glycine-Proline ratio (p = 0.035). Our results suggest that changes in human milk composition are associated with interactions between maternal and infant characteristics and pathophysiological factors. Future work should expand on these findings and further explore the link between hormonal profiles in human milk and infant outcomes

The ADIPS pilot national diabetes in pregnancy benchmarking programme

Background: To test the feasibility of benchmarking the care of women with pregnancies complicated by hyperglycaemia. Methods: A retrospective audit of volunteer diabetes services in Australia and New Zealand involving singleton pregnancies resulting in live births between 2014 and 2020. Ranges are shown and compared across services. Results: The audit included 10,144 pregnancies (gestational diabetes mellitus (GDM) = 8696; type 1 diabetes (T1D) = 435; type 2 diabetes (T2D) = 1013) from 11 diabetes services. Among women with GDM, diet alone was used in 39.4% (ranging among centres from 28.8-57.3%), metformin alone in 18.8% (0.4-43.7%), and metformin and insulin in 10.1% (1.5-23.4%); when compared between sites, all p 6.5% (48 mmol/mol)), 78.4% and 54.6%, respectively (p < 0.001). Conclusion: Management of maternal hyperglycaemia and pregnancy outcomes varied significantly. The maintenance and extension of this benchmarking service provides opportunities to identify policy and clinical approaches to improve pregnancy outcomes among women with hyperglycaemia in pregnancy

The analysis of clonal diversity and therapy responses using STAT3 mutations as a molecular marker in large granular lymphocytic leukemia

Peer reviewe